Infliximab, Azathioprine, or Combination Therapy for Crohn's Disease

N Engl J Med. 2010 Apr 15;362(15):1383-95. doi: 10.1056/NEJMoa0904492.

Abstract

Background: The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown.

Methods: In this randomized, double-blind trial, we evaluated the efficacy of infliximab monotherapy, azathioprine monotherapy, and the two drugs combined in 508 adults with moderate-to-severe Crohn's disease who had not undergone previous immunosuppressive or biologic therapy. Patients were randomly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0, 2, and 6 and then every 8 weeks plus daily oral placebo capsules; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the standard schedule; or combination therapy with the two drugs. Patients received study medication through week 30 and could continue in a blinded study extension through week 50.

Results: Of the 169 patients receiving combination therapy, 96 (56.8%) were in corticosteroid-free clinical remission at week 26 (the primary end point), as compared with 75 of 169 patients (44.4%) receiving infliximab alone (P=0.02) and 51 of 170 patients (30.0%) receiving azathioprine alone (P<0.001 for the comparison with combination therapy and P=0.006 for the comparison with infliximab). Similar numerical trends were found at week 50. At week 26, mucosal healing had occurred in 47 of 107 patients (43.9%) receiving combination therapy, as compared with 28 of 93 patients (30.1%) receiving infliximab (P=0.06) and 18 of 109 patients (16.5%) receiving azathioprine (P<0.001 for the comparison with combination therapy and P=0.02 for the comparison with infliximab). Serious infections developed in 3.9% of patients in the combination-therapy group, 4.9% of those in the infliximab group, and 5.6% of those in the azathioprine group.

Conclusions: Patients with moderate-to-severe Crohn's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy. (ClinicalTrials.gov number, NCT00094458.)

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Azathioprine / adverse effects
  • Azathioprine / therapeutic use*
  • Chi-Square Distribution
  • Crohn Disease / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Infliximab
  • Infusions, Intravenous
  • Logistic Models
  • Male
  • Remission Induction

Substances

  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Immunosuppressive Agents
  • Infliximab
  • Azathioprine

Associated data

  • ClinicalTrials.gov/NCT00094458